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ObjectivesTo investigate image-guided volumetric hyperthermia strategies using the ExAblate Body MR-guided focused ultrasound ablation system, involving mechanical transducer movement and sector-vortex beamforming.Materials and methodsAcoustic and thermal simulations were performed to investigate volumetric hyperthermia using mechanical transducer movement combined with sector-vortex beamforming, specifically for the ExAblate Body transducer. The system control in the ExAblate Body system was modified to achieve fast transducer movement and MR thermometry-based hyperthermia control, mechanical transducer movements and electronic sector-vortex beamforming were combined to optimize hyperthermia delivery. The experimental validation was performed using a tissue-mimicking phantom.ResultsThe developed simulation framework allowed for a parametric study with varying numbers of heating spots, sonication durations, and transducer movement times to evaluate the hyperthermia characteristics for mechanical transducer movement and sector-vortex beamforming. Hyperthermic patterns involving 2-4 sequential focal spots were analyzed. To demonstrate the feasibility of volumetric hyperthermia in the system, a tissue-mimicking phantom was sonicated with two distinct spots through mechanical transducer movement and sector-vortex beamforming. During hyperthermia, the average values of Tmax, T10, Tavg, T90, and Tmin over 200 s were measured within a circular ROI with a diameter of 10 pixels. These values were found to be 8.6, 7.9, 6.6, 5.2, and 4.5 °C, respectively, compared to the baseline temperature.ConclusionsThis study demonstrated the volumetric hyperthermia capabilities of the ExAblate Body system. The simulation framework developed in this study allowed for the evaluation of hyperthermia characteristics that could be implemented with the ExAblate MRgFUS system.

Since extracellular vesicles (EVs) have emerged as a promising drug delivery system, diverse methods have been used to load them with active pharmaceutical ingredients (API) in preclinical and clinical studies. However, there is yet to be an engineered EV formulation approved for human use, a barrier driven in part by the intrinsic heterogeneity of EVs. API loading is rarely assessed in the context of single vesicle measurements of physicochemical properties but is likely administered in a heterogeneous fashion to the detriment of a consistent product. Here, we applied a suite of single-particle resolution methods to determine the loading of rhodamine 6G (R6G) surrogate cargo mimicking hydrophilic small molecule drugs across four common API loading methods: sonication, electroporation, freeze-thaw cycling and passive incubation. Loading efficiencies and alterations in the physical properties of EVs were assessed, as well as co-localization with common EV-associated tetraspanins (i.e., CD63, CD81 and CD9) for insight into EV subpopulations. Sonication had the highest loading efficiency, yet significantly decreased particle yield, while electroporation led to the greatest number of loaded API particles, albeit at a lower efficiency. Moreover, results were often inconsistent between repeated runs within a given method, demonstrating the difficulty in developing a rigorous loading method that consistently loaded EVs across their heterogeneous subpopulations. This work highlights the significance of how chosen quantification metrics can impact apparent conclusions and the importance of single-particle characterization of EV loading.

PURPOSE OF REVIEW: Glioblastoma remains resistant to most conventional treatments. Despite scientific advances in the past three decades, there has been a dearth of effective new treatments. New approaches to drug delivery and clinical trial design are needed. RECENT FINDINGS: We discuss how the blood-brain barrier and tumor microenvironment pose challenges for development of effective therapies for glioblastoma. Next, we discuss treatments in development that aim to overcome these barriers, including novel drug designs such as nanoparticles and antibody-drug conjugates, novel methods of drug delivery, including convection-enhanced and intra-arterial delivery, and novel methods to enhance drug penetration, such as blood-brain barrier disruption by focused ultrasound and laser interstitial thermal therapy. Lastly, we address future opportunities, positing combination therapy as the best strategy for effective treatment, neoadjuvant and window-of-opportunity approaches to simultaneously enhance therapeutic effectiveness with interrogation of on-treatment biologic endpoints, and adaptive platform and basket trials as imperative for future trial design. New approaches to GBM treatment should account for the blood-brain barrier and immunosuppression by improving drug delivery, combining treatments, and integrating novel clinical trial designs.

Clinical drug administration aims to deliver drugs efficiently and safely to target tissues, organs, and cells, with the objective of enabling their therapeutic effects. Currently, the main approach to enhance a drugs effectiveness is ensuring its efficient delivery to the intended site. Due to the fact that there are still various drawbacks of traditional drug delivery methods, such as high toxicity and side effects, insufficient drug specificity, poor targeting, and poor pharmacokinetic performance, nanocarriers have emerged as a promising alternative. Nanocarriers possess significant advantages in drug delivery due to their size tunability and surface modifiability. Moreover, nano-drug delivery systems have demonstrated strong potential in terms of prolonging drug circulation time, improving bioavailability, increasing drug retention at the tumor site, decreasing drug resistance, as well as reducing the undesirable side effects of anticancer drugs. Numerous studies have focused on utilizing polysaccharides as nanodelivery carriers, developing delivery systems based on polysaccharides, or exploiting polysaccharides as tumor-targeting ligands to enhance the precision of nanoparticle delivery. These types of investigations have become commonplace in the academic literature. This review aims to elucidate the preparation methods and principles of polysaccharide gold nanocarriers. It also provides an overview of the factors that affect the loading of polysaccharide gold nanocarriers with different kinds of drugs. Additionally, it outlines the strategies employed by polysaccharide gold nanocarriers to improve the delivery efficiency of various drugs. The objective is to provide a reference for further development of research on polysaccharide gold nanodelivery systems.

Chemical pesticide delivery is a fundamental aspect of agriculture. However, the extensive use of pesticides severely endangers the ecosystem because they accumulate on crops, in soil, as well as in drinking and groundwater. New frontiers in nano-engineering have opened the door for precision agriculture. We introduced Tobacco mild green mosaic virus (TMGMV) as a viable delivery platform with a high aspect ratio and favorable soil mobility. In this work, we assess the use of TMGMV as a chemical nanocarrier for agriculturally relevant cargo. While plant viruses are usually portrayed as rigid/solid structures, these are "dynamic materials," and they "breathe" in solution in response to careful adjustment of pH or bathing media [e.g., addition of solvent such as dimethyl sulfoxide (DMSO)]. Through this process, coat proteins (CPs) partially dissociate leading to swelling of the nucleoprotein complexes-allowing for the infusion of active ingredients (AI), such as pesticides [e.g., fluopyram (FLP), clothianidin (CTD), rifampicin (RIF), and ivermectin (IVM)] into the macromolecular structure. We developed a "breathing" method that facilitates inter-coat protein cargo loading, resulting in up to  ~ 1000 AIs per virion. This is of significance since in the agricultural setting, there is a need to develop nanoparticle delivery strategies where the AI is not chemically altered, consequently avoiding the need for regulatory and registration processes of new compounds. This work highlights the potential of TMGMV as a pesticide nanocarrier in precision farming applications; the developed methods likely would be applicable to other protein-based nanoparticle systems.

Development of smart drug delivery systems (DDSs) for effective delivering drugs to targeted areas and achieving controlled drug release (CDR) is critical for cancer chemotherapy. The purpose of this study is synthesis of polydopamine (PDA) nanocapsules and analyze the adsorption and release properties of doxorubicin (DOX). PDA nanocapsules are manufactured using hard template approach. The influence of various parameters such as pH, adsorption time, and initial DOX content on the adsorption and release process is investigated. The resulting adsorption isotherm is consistent with the Langmuir isotherm, indicating that DOX adsorption on PDA nanocapsules is homogenous, uniform, and monolayer. PDA nanocapsules have an adsorption capacity of 689.6 mg g−1 under alkaline conditions, which is attributed to phenol group deprotonation mechanism and electrostatic repulsion. The adsorption kinetics are more consistent with the pseudo‐second‐order model. Furthermore, raising initial concentration of DOX results in a greatly increased adsorption capacity due to a larger driving force. Among the several parameters that can influence the pace and degree of DOX loading and release, local pH is regarded as a significant environmental component in the processes. Thus, pH‐responsive PDA nanocapsules have a significant potential for usage in locations with aberrant pH level, such as cancer tissue. [ABSTRACT FROM AUTHOR]

The development of safe and efficient delivery systems for targeted and controlled release of therapeutic agents has become a major focus in pharmacotherapy. The colon is one organ that serves as an optimal site for the absorption of protein and peptide drugs, offering significant potential for both localized and systemic therapies. However, effective drug delivery is challenged by the need to protect these drugs from premature absorption and maintain their stability across the varying pH levels of the gastrointestinal tract. In this study, we introduce, for the first time, a fully natural hydrogel system composed of N-acetylated chitosan and alginate, crosslinked using a phenylalanine-phenylalanine dipeptide. The hydrogel demonstrates a unique swelling behavior, allowing for a solvent-free drug-loading method and pH-sensitive release properties. In a colon-simulated pH environment, the hydrogel achieved a high drug release efficiency, with 77.6% of the tested drug sulfasalazine and 51% of hydrocortisone over 5 hours. These findings underscore hydrogel's potential as a promising drug delivery carrier for targeted gastrointestinal treatments, with the capacity to enhance the efficacy of current therapeutic options. [ABSTRACT FROM AUTHOR]

Poly(N‐isopropylacrylamide) (PNIPAM) is a versatile polymer known for its phase transition properties, exhibiting a lower critical solution temperature (LCST) of approximately 32°C. Below this temperature, PNIPAM is hydrophilic, while above it, the polymer becomes hydrophobic, making it ideal for thermosensitive drug delivery systems (DDSs). In tissue engineering, PNIPAM provides a biocompatible, nontoxic and stimuli‐responsive surface for cell culture. Its nontoxic nature ensures safety in medical applications. PNIPAM enhances biosensing diagnostics through its affinity for biomolecules, improving accuracy. Widely used in hydrogels, smart textiles, soft robotics and various medical applications, PNIPAM adapts to environmental changes. Its straightforward synthesis allows for the creation of diverse copolymers and composites, applicable in selective reactions and conjugations with fluorescent tags or chemical modifications. PNIPAM's versatility extends to pH‐responsive alternatives, broadening its application spectrum. Practical examples include phase separation in water treatment and cleaning processes. This discussion explores PNIPAM's biomedical and drug delivery applications, particularly in cancer treatment, photothermal therapy (PTT) and photodynamic therapy (PDT), gene delivery and medical imaging. Additionally, it highlights PNIPAM's noncancerous applications, such as small interfering RNA (siRNA) targeting of oncogenes and detailed imaging of deep and tumour tissues. [ABSTRACT FROM AUTHOR]

Bioceramics composed of calcium and magnesium silicates have garnered increasing attention for the development of porous scaffolds in bone tissue engineering (BTE). This heightened interest is primarily attributed to their remarkable bioactivity and their capacity to form strong bonds with hard tissue. Fabricating nanocomposite scaffolds is a recognized approach for improving the characteristics of scaffolds used in BTE. This research investigates the mechanical and biological properties, antibacterial activity, and drug-release characteristics of scaffolds composed of akermanite (AKT), monticellite (MON), and monticellite-akermanite (MON-AKT). These scaffolds were fabricated utilizing the space holder process. Additionally, the in vitro drug release profile and antimicrobial activity of Azithromycin (AZT)-loaded MON-AKT composite scaffolds were investigated. The findings showed that the Mon-15 wt% AKT nanocomposite scaffold had the highest density, the smallest grain and micropore sizes, and the lowest porosity. In contrast, integrating AKT into MON-based composite scaffolds resulted in materials characterized by high mechanical strength and stability within physiological environments. The MON-AKT nanocomposite scaffolds exhibited cytocompatibility and demonstrated a high level of alkaline phosphatase (ALP) activity in osteogenic studies. Furthermore, antimicrobial activity assessments revealed that the AZT-encapsulated MON-AKT composite scaffolds effectively inhibited the growth of both S. aureus and E. coli bacteria. The outcomes showed that the antibacterial efficacy of the scaffold depends on both the amount of AZT and the type of bacteria. Overall, MON-AKT/3AZT scaffolds exhibited significantly superior bacterial inhibition compared to other scaffolds, making it a promising option for treating bone tissue defects. [ABSTRACT FROM AUTHOR]

Messenger RNA (mRNA) has emerged as an attractive therapeutic molecule for a plethora of clinical applications. For in vivo functionality, mRNA therapeutics require encapsulation into effective, stable, and safe delivery systems to protect the cargo from degradation and reduce immunogenicity. Here, a bioengineering platform for efficient mRNA loading and functional delivery using bionormal nanoparticles, extracellular vesicles (EVs), is established by expressing a highly specific RNA‐binding domain fused to CD63 in EV producer cells stably expressing the target mRNA. The additional combination with a fusogenic endosomal escape moiety, Vesicular Stomatitis Virus Glycoprotein, enables functional mRNA delivery in vivo at doses substantially lower than currently used clinically with synthetic lipid‐based nanoparticles. Importantly, the application of EVs loaded with effective cancer immunotherapy proves highly effective in an aggressive melanoma mouse model. This technology addresses substantial drawbacks currently associated with EV‐based nucleic acid delivery systems and is a leap forward to clinical EV applications. [ABSTRACT FROM AUTHOR]

Myocardial ischemia/reperfusion injury (MI/RI) generates reactive oxygen species (ROS) and initiates inflammatory responses. Traditional therapies targeting specific cytokines or ROS often prove inadequate. An innovative drug delivery system (DDS) is developed using neutrophil decoys (NDs) that encapsulate 18β‐glycyrrhetinic acid (GA) within a hydrolyzable oxalate polymer (HOP) and neutrophil membrane vesicles (NMVs). These NDs are responsive to hydrogen peroxide (H2O2), enabling controlled GA release. Additionally, NDs adsorb inflammatory factors, thereby reducing inflammation. They exhibit enhanced adhesion to inflamed endothelial cells (ECs) and improved penetration. Once internalized by cardiomyocytes through clathrin‐mediated endocytosis, NDs protect against ROS‐induced damage and inhibit HMGB1 translocation. In vivo studies show that NDs preferentially accumulate in injured myocardium, reducing infarct size, mitigating adverse remodeling, and enhancing cardiac function, all while maintaining favorable biosafety profiles. This neutrophil‐based system offers a promising targeted therapy for MI/RI by addressing both inflammation and ROS, holding potential for future clinical applications. [ABSTRACT FROM AUTHOR]

Peptide coacervates self‐assembling via liquid‐liquid phase separation are appealing intracellular delivery vehicles of macromolecular therapeutics (proteins, DNA, mRNA) owing to their non‐cytotoxicity, high encapsulation capacity, and efficient cellular uptake. However, the mechanisms by which these viscoelastic droplets cross the cellular membranes remain unknown. Here, using multimodal imaging, data analytics, and biochemical inhibition assays, we identify the key steps by which droplets enter the cell. We find that the uptake follows a non‐canonical pathway and instead integrates essential features of macropinocytosis and phagocytosis, namely active remodeling of the actin cytoskeleton and appearance of filopodia‐like protrusions. Experiments using giant unilamellar vesicles show that the coacervates attach to the bounding membrane in a charge‐ and cholesterol‐dependent manner but do not breach the lipid bilayer barrier. Cell uptake in the presence of small molecule inhibitors – interfering with actin and tubulin polymerization – confirm the active role of cytoskeleton remodeling, most prominently evident in electron microscopy imaging. These findings suggest a peculiar internalization mechanism for viscoelastic, glassy coacervate droplets combining features of non‐specific uptake of fluids by macropinocytosis and particulate uptake of phagocytosis. The broad implications of this study will enable to enhance the efficacy and utility of coacervate‐based strategies for intracellular delivery of macromolecular therapeutics. [ABSTRACT FROM AUTHOR]

Aim: The study aims to improve glioblastoma multiforme (GBM) treatment by combining temozolomide (TMZ) and quercetin (Qct), using folic acid (FA)-conjugated exosomes to overcome TMZ resistance and enhance blood–brain barrier (BBB) penetration. Methods: Exosomes were isolated and after characterizing and modifying their surfaces with FA, drug loading of TMZ and Qct into exosomes was done. In vitro assays, including cell viability tests, RT-PCR, Western-blotting and flow-cytometry, were performed using U87MG and U251MG GBM cell lines. In vivo analysis included administering exosome-drug formulations to glioblastoma-bearing Wistar rats, monitored through optical imaging and PET scans, followed by post-mortem immunohistochemistry and histological examination. Results: The results showed successful exosome isolation and FA conjugation, with drug release studies indicating accelerated release of TMZ and Qct in acidic conditions, enhancing cytotoxicity. Immunofluorescence indicated greater exosome uptake in GBM cells due to FA conjugation. Cell viability assays demonstrated increased toxicity of the combination therapy, correlating with elevated apoptosis. In vivo studies revealed significant tumor size reduction, alongside increased apoptosis and reduced angiogenesis, particularly in the TMZ-Qct-Exo-FA group. Conclusion: FA-conjugated exosomes loaded with TMZ and Qct represent a promising strategy to enhance GBM treatment efficacy by improving drug delivery, apoptosis induction and inhibiting the PI3K/Akt/mTOR pathway. Graphical Abstract Schematic illustration of exosome isolation and conjugation followed by loading with temozolomide (TMZ) and Quercetin (Qct) for glioblastoma therapy. (A) Process of isolating exosomes and conjugating them with folic acid loaded with TMZ and Qct (B) Function of exosomes conjugated with folic acid in a rat model of glioblastoma (C) Mechanism of how exosomes bearing TMZ and Qct work inside the glioblastoma cell line. Article highlights The study emphasizes the successful use of exosome encapsulation to enhance the delivery of temozolomide (TMZ) and quercetin (Qct) across the blood–brain barrier (BBB), improving drug stability for glioblastoma multiforme (GBM) therapy. Encapsulating TMZ and Qct within exosomes (TMZ-Qct-Exo) showed significantly greater potential in reducing GBM cell viability compared with their unencapsulated counterparts, suggesting an effective approach against TMZ resistance. The introduction of folic acid-conjugated exosomes (TMZ-Qct-Exo-FA) enhanced the targeting of GBM cells, leading to better cellular uptake and improved therapeutic outcomes marked by greater apoptosis and increased caspase-3 levels. The combined treatment effectively inhibited the PI3K/Akt/mTOR signaling pathway, vital for tumor growth and survival, thereby boosting the anti-tumor effects of the TMZ-Qct-Exo-FA treatment. In vivo studies demonstrated that the TMZ-Qct-Exo-FA formulation resulted in superior tumor targeting, significantly reduced tumor size and higher levels of apoptotic markers compared with alternative treatment methods. The findings highlight that exosome-mediated drug delivery could serve as a promising strategy to circumvent resistance mechanisms commonly associated with TMZ in GBM treatment. The research indicates that combining exosome technology with conventional chemotherapy could pave the way for new therapeutic modalities in the treatment of aggressive brain tumors like GBM. The use of folic acid as a targeting moiety suggests an innovative approach to enhance specificity in drug delivery systems directed at tumor cells. These results underscore the need for further clinical studies to explore the full potential of exosome-mediated delivery systems in enhancing the effectiveness of existing cancer therapies. [ABSTRACT FROM AUTHOR]

The type of algorithm employed to predict drug release from liposomes plays an important role in affecting the accuracy. In recent years, Machine Learning (ML) has shown potential for modeling complex drug delivery systems and predicting drug release dynamics with a greater degree of precision. In this regard, Random Forest (RF) and Support Vector Machine (SVM) are two ML algorithms that have been extensively applied in various biomedical and drug delivery contexts. Yet, direct comparisons of their predictive accuracy in modeling ultrasound-triggered drug release from liposomes remain limited. Existing studies predominantly focus on drug release under static conditions or with limited external stimuli rather than the dynamic, nonlinear responses observed under ultrasound exposure. Objective: This study presents a comparative analysis of RF and SVM for predicting calcein release from ultrasound-triggered, targeted liposomes under varied low-frequency ultrasound (LFUS) power densities (6.2, 9, and 10 mW/cm2). Methods: Liposomes loaded with calcein and targeted with seven different moieties (cRGD, estrone, folate, Herceptin, hyaluronic acid, lactobionic acid, and transferrin) were synthesized using the thin-film hydration method. The liposomes were characterized using Dynamic Light Scattering and Bicinchoninic Acid assays. Extensive data collection and preprocessing were performed. RF and SVM models were trained and evaluated using mean absolute error (MAE), mean squared error (MSE), coefficient of determination (R²), and the a20 index as performance metrics. Results: RF consistently outperformed SVM, achieving R2 scores above 0.96 across all power densities, particularly excelling at higher power densities and indicating a strong correlation with the actual data. Conclusion: RF outperforms SVM in drug release prediction, though both show strengths and apply based on specific prediction needs. [ABSTRACT FROM AUTHOR]

Small soft robotic systems are being explored for myriad applications in medicine. Specifically, magnetically actuated microrobots capable of remote manipulation hold significant potential for the targeted delivery of therapeutics and biologicals. Much of previous efforts on microrobotics have been dedicated to locomotion in aqueous environments and hard surfaces. However, our human bodies are made of dense biological tissues, requiring researchers to develop new microrobotics that can locomote atop tissue surfaces. Tumbling microrobots are a sub-category of these devices capable of walking on surfaces guided by rotating magnetic fields. Using microrobots to deliver payloads to specific regions of sensitive tissues is a primary goal of medical microrobots. Central nervous system (CNS) tissues are a prime candidate given their delicate structure and highly region-specific function. Here we demonstrate surface walking of soft alginate capsules capable of moving on top of a rat cortex and mouse spinal cord ex vivo , demonstrating multi-location small molecule delivery to up to six different locations on each type of tissue with high spatial specificity. The softness of alginate gel prevents injuries that may arise from friction with CNS tissues during millirobot locomotion. Development of this technology may be useful in clinical and preclinical applications such as drug delivery, neural stimulation, and diagnostic imaging. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) bone metastasis poses a significant clinical challenge due to its impact on patient prognosis and quality of life. Curcumin (CUR), a natural polyphenol compound found in turmeric, has shown potential in cancer therapy due to its anti-inflammatory, antioxidant, and anticancer properties. However, its metabolic instability and hydrophobicity have hindered its clinical applications, leading to a short plasma half-life, poor absorption, and low bioavailability. To enhance the drug-like properties of CUR, nanotechnology-based delivery strategies have been employed, utilizing polymeric, lipidic, and inorganic nanoparticles (NPs). These approaches have effectively overcome CUR's inherent limitations by enhancing its stability and cellular bioavailability both in vitro and in vivo. Moreover, targeting molecules with high selectivity towards bone metastasized breast cancer cells can be used for site specific delivery of curcumin. Alendronate (ALN), a bone-seeking bisphosphonate, is one such moiety with high selectivity towards bone and thus can be effectively used for targeted delivery of curcumin loaded nanocarriers. This review will detail the process of bone metastasis in BC, elucidate the mechanism of action of CUR, and assess the efficacy of nanotechnology-based strategies for CUR delivery. Specifically, it will focus on how these strategies enhance CUR's stability and improve targeted delivery approaches in the treatment of BC bone metastasis. [ABSTRACT FROM AUTHOR]

This article explores the multifaceted potential of pullulan‐based films across food‐packaging, pharmaceutical, biomedical, and cosmetic applications. In food‐packaging, pullulan films serve as transparent, flexible, and high‐oxygen barrier materials, effectively preserving the freshness and quality of a wide range of fruits and vegetables. Edible pullulan films extend the shelf life and enhance food safety, while active pullulan films inhibit microbial growth and oxidation, thus supports food preservation. In the pharmaceutical industry, pullulan‐based films offer promising solutions for oral drug delivery, providing biodegradable and rapid disintegration for enhanced solubility and bioavailability of drugs. Additionally, due to their mechanical strength, biocompatibility, and antimicrobial properties, pullulan films demonstrate potential in wound dressings and tissue engineering applications. Furthermore, pullulan's utility extends to the cosmetic industry, where it is used widely in various ingredients in skincare products, cosmetics, and personal care items. Its moisturizing, stabilizing, and film‐forming properties make pullulan an attractive component in the industry. Future research directions should focus on cost‐effective production methods and expanding industrial applications to further enhance their effectiveness and versatility. This in‐depth analysis highlights the significant potential of pullulan‐based films across multiple industries and underscores the importance of continued research and development efforts to fully unlock their diverse applications and benefits. [ABSTRACT FROM AUTHOR]

High dose-rate brachytherapy presents a promising therapeutic avenue for prostate cancer management, involving the temporary implantation of catheters which deliver radioactive sources to the cancerous site. However, as catheters puncture and penetrate the prostate, tissue deformation is evident which may affect the accuracy and efficiency of the treatment. In this work, a data-driven in silico modelling procedure is proposed to simulate brachytherapy while accounting for prostate biomechanics. Comprehensive magnetic resonance and transrectal ultrasound images acquired prior, during and post brachytherapy are employed for model personalisation, while the therapeutic procedure is simulated via sequential insertion of multiple catheters in the prostate gland. The medical imaging data are also employed for model evaluation, thus, demonstrating the potential of the proposed in silico procedure to be utilised pre- and intra-operatively in the clinical setting. [ABSTRACT FROM AUTHOR]

Orthopedic implants have faced challenges in treating bone defects due to various factors, including inadequate osseointegration, oxidative stress, bacterial infection, immunological rejection, and poor individualized treatment. These challenges profoundly affect both the results of treatment and patients' daily lives. There is great promise for the layer-by-layer (LbL) assembly method in tissue engineering. The method primarily relies on electrostatic attraction and entails the consecutive deposition of electrolyte complexes with opposite charges onto a substrate, leading to the formation of homogeneous single layers that can be quickly deposited to produce nanolayer films. LbL has attracted considerable interest as a coating technology because of its ease of production, cost-effectiveness, and capability to apply diverse biomaterial coatings without compromising the primary bio-functional properties of the substrate materials. This review will look into the fundamentals and evolution of LbL in orthopedics, provide an analysis of the chemical strategy used to prepare bone implants with LbL and introduce the application of LbL bone implants in orthopedics over recent years. Among the many potential uses of LbL, such as the implementation of sustained-release and programmed drug delivery, which in turn promotes the osseointegration and the development of new blood vessels, as well as antibacterial, antioxidant, and other similar applications. In addition, we offer a thorough examination of cell behavior and biomaterial interaction to facilitate the advancement of next-generation LbL films for tissue engineering. [ABSTRACT FROM AUTHOR]

Materials data science and machine learning (ML) are pivotal in advancing cancer treatment strategies beyond traditional methods like chemotherapy. Nanotherapeutics, which merge nanotechnology with targeted drug delivery, exemplify this advancement by offering improved precision and reduced side effects in cancer therapy. The development of these nanotherapeutic agents depends critically on understanding nanoparticle (NP) properties and their biological interactions, often analyzed through molecular dynamics (MD) simulations. This study enhances these analyses by integrating ML with MD simulations, significantly improving both prediction accuracy and computational efficiency. We introduce a comprehensive three-stage methodology for predicting the solvent-accessible surface area (SASA) of NPs, which is crucial for their therapeutic efficacy. The process involves training an ML model to forecast the many-body tensor representation (MBTR) for future time steps, applying data augmentation to increase dataset realism, and refining the SASA predictor with both augmented and original data. Results demonstrate that our methodology can predict SASA values 299 time steps ahead with a 40-fold speed improvement and a 25% accuracy increase over existing methods. Importantly, it provides a 300-fold increase in computational speed compared to traditional simulation techniques, offering substantial cost and time savings for nanotherapeutic research and development. [ABSTRACT FROM AUTHOR]

Nanoparticles are attractive therapeutic tools due to their distinctive characteristics, including more accurate drug delivery, improved bioavailability, and enhanced targeted therapy. This review offers a comprehensive analysis of the therapeutic potentials of cutting-edge nanoparticles as demonstrated in human clinical trials, based on empirical evidence. Through systematic searches of major scientific databases, relevant studies published up to March 2024 were included, focusing on clinical trials utilizing advanced nanoparticles for therapeutic purposes. The review discusses the diverse applications of nanoparticles in oncology, infectious diseases, neurology, and other medical fields. Additionally, it scrutinizes the safety profiles, efficacy outcomes, and challenges associated with nanoparticle-based therapies. The findings underscore significant progress in translating nanoparticle research into clinical practice and highlight the potential of these innovative platforms to revolutionize medical treatments. This review contributes valuable insights into the growing field of nanoparticle-based therapeutics, fostering a deeper understanding of their clinical applications and implications in medical practice. [ABSTRACT FROM AUTHOR]

Conventional chemotherapeutic agents are limited by their lack of targeting and penetration and their short retention time, and chemotherapy might induce an immune suppressive environment. Peptide self‐assembly can result in a specific morphology, and the resulting morphological changes are stimuli responsive to the external environment, which is important for drug permeation and retention of encapsulated chemotherapeutic agents. In this study, a polypeptide (Pep1) containing the peptide sequences PLGLAG and RGD that is responsive to matrix metalloproteinase 2 (MMP‐2) was successfully developed. Pep1 underwent a morphological transformation from a spherical structure to aggregates with a high aspect ratio in response to MMP‐2 induction. This drug delivery system (DI/Pep1) can transport doxorubicin (DOX) and indomethacin (IND) simultaneously to target tumor cells for subsequent drug release while extending drug retention within tumor cells, which increases immunogenic cell death and facilitates the immunotherapeutic effect of CD4+ T cells. Ultimately, DI/Pep1 attenuated tumor‐associated inflammation, enhanced the body's immune response, and inhibited breast cancer growth by combining the actions of DOX and IND. Our research offers an approach to hopefully enhance the effectiveness of cancer treatment. [ABSTRACT FROM AUTHOR]

Hydrogels have been used in the clinic since the late 1980s with broad applications in drug delivery, cosmetics, tissue regeneration, among many other areas. The past three decades have witnessed rapid advances in the fields of polymer chemistry, crosslinking approaches, and hydrogel fabrication methods, which have collectively brought many new hydrogel products, either injectable or non‐injectable, to clinical studies. In an article published in 2020 entitled "Hydrogels in the clinic", we reviewed the clinical landscape and translational challenges of injectable hydrogels. Here, we provide an update on the advances in the field and also extend the scope to include non‐injectable hydrogels. We highlight recently approved hydrogel products, provide an update on the clinical trials of injectable hydrogels, and discuss active clinical trials of topically applied and implantable hydrogels. [ABSTRACT FROM AUTHOR]

Antibody‐drug conjugates (ADCs), chemotherapeutic agents conjugated to an antibody to enhance their targeted delivery to tumors, represent a significant advancement in cancer therapy. ADCs combine the precise targeting capabilities of antibodies and the potent cell‐killing effects of chemotherapy, allowing for enhanced cytotoxicity to tumors while minimizing damage to healthy tissues. Here, we provide an overview of the current clinical landscape of ADCs, highlighting 11 U.S. Food and Drug Administration (FDA)‐approved products and discussing over 500 active clinical trials investigating newer ADCs. We also discuss some key challenges associated with the clinical translation of ADCs and highlight emerging strategies to overcome these hurdles. Our discussions will provide useful guidelines for the future development of safer and more effective ADCs for a broader range of indications. [ABSTRACT FROM AUTHOR]

The alarming rise in chronic diseases worldwide highlights the urgent need to overcome the limitations of conventional drug delivery systems. In this context, osmotic pumps are able to release drugs by differential osmotic pressure, achieving a controlled rate independent of physiological factors and reducing the dosing frequency. As osmotic pumps are based on the phenomenon of osmosis, the choice of high osmolality draw solutions (DSs) is a critical factor in the successful delivery of the target drug. Therefore, one alternative that has received particular attention is the formulation of DSs with magnetic nanoparticles (MNPs) due to their easy recovery, negligible reverse solute flux (RSF), and their possible tailor-made functionalization to generate high osmotic gradients. In this work, the possible integration of DSs formulated with MNPs in controlled drug delivery systems is discussed for the first time. In particular, the main potential advantages that these novel medical devices could offer, including improved scalability, regeneration, reliability, and enhanced drug delivery performance, are provided and discussed. Thus, the results of this review may demonstrate the potential of MNPs as osmotic agents, which could be useful for advancing the design of osmotic pump-based drug delivery systems. [ABSTRACT FROM AUTHOR]

To overcome chondrosarcoma's (CHS) high chemo- and radioresistance, we used polyethylene glycol-encapsulated iron oxide nanoparticles (IONPs) for the controlled delivery of the chemotherapeutic doxorubicin (IONPDOX) to amplify the cytotoxicity of proton radiation therapy. Human 2D CHS SW1353 cells were treated with protons (linear energy transfer (LET): 1.6 and 12.6 keV/µm) with and without IONPDOX. Cell survival was assayed using a clonogenic test, and genotoxicity was tested through the formation of micronuclei (MN) and γH2AX foci, respectively. Morphology together with spectral fingerprints of nuclei were measured using enhanced dark-field microscopy (EDFM) assembled with a hyperspectral imaging (HI) module and an axial scanning fluorescence module, as well as scanning electron microscopy (SEM) coupled with energy-dispersive X-Ray spectroscopy (EDX). Cell survival was also determined in 3D SW3153 spheroids following treatment with low-LET protons with/without the IONPDOX compound. IONPDOX increased radiosensitivity following proton irradiation at both LETs in correlation with DNA damage expressed as MN or γH2AX. The IONPDOX–low-LET proton combination caused a more lethal effect compared to IONPDOX–high-LET protons. CHS cell biological alterations were reflected by the modifications in the hyperspectral images and spectral profiles, emphasizing new possible spectroscopic markers of cancer therapy effects. Our findings show that the proposed treatment combination has the potential to improve the management of CHS. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to formulate Citrus limon fruit rind's essential oil (EO) and to analyze its impact on breast cancer cells. Materials and Methods: Initially, the cytotoxicity of EO (0.09-9 µg/ml) and doxorubicin (0.5-5 µM) on MCF-7, SK-BR-3, and MDA-MB-231 breast cancer cells was assessed using the MTT assay following 24-72 hr treatment. The cells were then treated with niosomes containing 4.5 µg/ml EO and 0.5 µM doxorubicin for 48 hr. Flow cytometry, migration assay, and RT-qPCR were used to study the cell behavior. Results: MTT results indicated that both EO and doxorubicin alone exhibited severe cytotoxicity (viability ≤ 30%) towards all three cells after 48 hr . When treated with encapsulated EO, the apoptotic death rate in MCF-7, MDA-MB-231, and SK-BR-3 cells was substantially diminished to 14%, 28%, and 9%, respectively. Similarly, encapsulated doxorubicin induced mild apoptotic death in these cells. Encapsulated EO and doxorubicin significantly prevented the migration of all cells. Following treatment with the encapsulated EO, a notable reduction in the expression of VIM, SLUG, SNAIL, and JUN, which are promoters of cancer cell invasion, was seen. Conversely, the expression of the FAS receptor, an active participant in the extrinsic apoptosis pathway, increased (p<0.01). Conclusion: Lemon EO has apoptotic and anti-migratory effects on breast cancer cells, comparable to that of doxorubicin. Utilizing niosome as an efficient delivery modality effectively mitigates the adverse effects of EO and can be used for in vivo delivery of it to cancer cells. [ABSTRACT FROM AUTHOR]

The biosynthesis of bacterial cellulose (BC) is significantly influenced by the type of carbon source available in the growth medium, which in turn dictates the material's final properties. This study systematically investigates the effects of five carbon sources—raffinose (C18H32O16), sucrose (C12H22O11), glucose (C6H12O6), arabinose (C5H10O5), and glycerol (C3H8O3)—on BC production by Komagataeibacter hansenii. The varying molecular weights and structural characteristics of these carbon sources provide a framework for examining their influence on BC yield, fiber morphology, and network properties. BC production was monitored through daily measurements of optical density and pH levels in the fermentation media from day 1 to day 14, providing valuable insights into bacterial growth kinetics and cellulose synthesis rates. Scanning electron microscopy (SEM) was used to elucidate fibril diameter and pore size distribution. Wide-angle X-ray scattering (WAXS) provided a detailed assessment of crystallinity. Selected BC pellicles were further processed via freeze-drying to produce a foam-like material that maximally preserves the natural three-dimensional structure of BC, facilitating the incorporation and release of lidocaine hydrochloride (5%), a widely used local anesthetic. The lidocaine-loaded BC foams exhibited a sustained and controlled release profile over 14 days in simulated body fluid, highlighting the importance of the role of carbon source selection in shaping the BC network architecture and its impact on drug release profile. These results highlight the versatility and sustainability of BC as a platform for wound healing and drug delivery applications. The tunable properties of BC networks provide opportunities for optimizing therapeutic delivery and improving wound care outcomes, positioning BC as an effective material for enhanced wound management strategies. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are gaining interest in regenerative medicine and biomaterials have been shown to extend EV bioavailability following delivery. Herein, the labeling of both hydrogels and EVs is reported to better understand hydrogel design for sustained EV release into tissues. Shear‐thinning hydrogels are engineered using guest–host (i.e., adamantane–cyclodextrin) modifications to hyaluronic acid (GH), as well as GH hydrogels with the addition of gelatin crosslinked via transglutaminase (GH+Gel) to temporally control hydrogel properties. When labeled with a near‐IR dye and injected into rat myocardial tissue, the GH+Gel hydrogel is retained (>14 days) longer than the GH hydrogel alone (≈7 days), likely due to the added gelatin network. To overcome challenges associated with common EV labeling methods, a highly versatile metabolic labeling methodology is utilized via the incorporation of N‐azidoacetylmannosamine‐tetraacylated during EV synthesis to introduce azide groups that can then be reacted with DBCO dyes. When injected in saline, EVs are cleared within 24 h in hearts; however, hydrogels enhance EV retention, with levels based on hydrogel degradation behavior, namely, >14 days for GH+Gel hydrogel and ≈7 days for GH hydrogel alone. These findings support the use of hydrogels in EV therapies. [ABSTRACT FROM AUTHOR]

Alpha-lipoic acid (ALA) has garnered significant attention for its potential therapeutic benefits across a wide spectrum of health conditions. Despite its remarkable antioxidant properties, ALA is hindered by challenges such as low bioavailability, short half-life, and unpleasant odor. To overcome these limitations and enhance ALA's therapeutic efficacy, various nanoparticulate drug delivery systems have been explored. This comprehensive review evaluates the application of different nanoparticulate carriers, including lipid-based nanoparticles (solid lipid nanoparticles, niosomes, liposomes, nanostructured lipid carriers (NLCs), and micelles), nanoemulsions, polymeric nanoparticles (nanocapsules, PEGylated nanoparticles, and polycaprolactone nanoparticles), films, nanofibers, and gold nanoparticles, for ALA delivery. Each nanoparticulate system offers unique advantages, such as improved stability, sustained release, enhanced bioavailability, and targeted delivery. For example, ALA-loaded SLNs demonstrated benefits for skin care products and skin rejuvenation. ALA encapsulated in niosomes showed potential for treating cerebral ischemia, a condition largely linked to stroke. ALA-loaded cationic nanoemulsions showed promise for ophthalmic applications, reducing vascular injuries, and corneal disorders. Coating liposomes with chitosan further enhanced stability and performance, promoting drug absorption through the skin. This review provides a comprehensive overview of the advancements in nanoparticulate delivery systems for ALA, highlighting their potential to overcome the limitations of ALA administration and significantly enhance its therapeutic effectiveness. These innovative approaches hold promise for the development of improved ALA-based treatments across a broad spectrum of health conditions. [ABSTRACT FROM AUTHOR]

Poly(vinyl alcohol) (PVA) based hydrogels have gained more interest in the field of biomaterials because of their many biomedical uses (i.e., wound healing, drug delivery, and tissue engineering) and intrinsic physicochemical and biological characteristics. They can be made using a variety of synthetic techniques, but all of them are very time-consuming. Among them, photopolymerization also referred to as light-induced polymerization, has drawn a lot of attention because of its benefits, which include not requiring the use of solvents, easy and quick network formation, energy efficiency, quick processing, control over both space and time and reliability of crosslinking density and matrix strength. Ultraviolet (UV)-curable hydrogels containing PVA as a main component are gaining interest because of their excellent properties, including biodegradability, biocompatibility, less cytotoxicity and remarkable mechanical strength. This review highlights the significance of UV curable systems and their components, types, advantages and disadvantages of photoinitiators (PIs), UV curable monomers and their structures, properties of UV-cured PVA hybrid hydrogels, and their characterizations and applications in different fields. The photopolymerization mechanisms, tunable properties, and unique advantages of these hydrogels have been explored in detail. Furthermore, it sheds light on recent advancements in PVA-based hydrogels research and future exploration in this domain. [ABSTRACT FROM AUTHOR]

[Display omitted] Breast cancers that overexpress human epidermal growth factor receptor 2 (HER2) have poor prognosis. Moreover, available chemotherapies cause numerous side effects due to poor selectivity. To advance more effective and safer therapies for HER2-positive breast cancer, we explored the fusion of drug delivery technology and immunotherapy. Our research led to the design of immunocubosomes loaded with panobinostat and functionalized with trastuzumab antibodies, enabling precise targeting of breast cancer cells that overexpress HER2. We characterised the nanostructure of cubosomes using small-angle X-ray scattering (SAXS), cryo-transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS). Moreover, we confirmed the integrity of the trastuzumab antibodies on the immunocubosomes by Fourier-transform infrared spectroscopy (FTIR) and sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Additionally, we found that panobinostat-loaded immunocubosomes were more cytotoxic, and in an uptake-dependant manner, towards a HER2-positive breast cancer cell line (SKBR3) compared to a cell line representing healthy cells (L929). These results support that the functionalization of cubosomes with antibodies enhances both the effectiveness of the loaded drug and its selectivity for targeting HER2-positive breast cancer cells. [ABSTRACT FROM AUTHOR]

Treatment of triple-negative breast cancer (TNBC) poses significant challenges due to its propensity for metastasis. A key impediment lies in the suppressive immune microenvironment, which fosters tumor progression. This study introduces an approach employing a dual immune-stimulatory CD73 antibody-polymeric cytotoxic drug complex (αCD73-PLG-MMAE). This complex is designed for targeted eradication of TNBC while modulating tumor immunity through mechanisms such as immunogenic cell death (ICD) and interference with the adenosine signaling pathway. By enhancing antitumor immune responses, this strategy offers a highly effective means of treating TNBC and mitigating metastasis. The complex is synthesized by combining αCD73 with poly(L -glutamic acid) (PLG) grafted Fc binding peptides (Fc-III-4C) and Val-Cit-PAB-monomethyl auristatin E (MMAE), exploiting the affinity between αCD73 and Fc-III-4C. αCD73 selectively targets CD73 molecules on both tumor and immune suppressive cells, thereby inhibiting the adenosine pathway. Meanwhile, Val-Cit-PAB-MMAE, activated by cathepsin B, triggers selective release of MMAE, inducing ICD in tumor cells. In a 4T1 tumor model, αCD73-PLG-MMAE significantly enhances drug accumulation in tumors by 4.13-fold compared to IgG-PLG-MMAE, leading to suppression of tumor growth and metastasis. Furthermore, it synergistically augments the antitumor effects of αPD-1, resulting in a tumor inhibition rate of 92 % as compared to 21 % with αPD-1 alone. This study thus presents a pioneering therapeutic strategy for TNBC, emphasizing the potential of targeted immunomodulation in cancer treatment. Antibody-drug conjugate (ADC) therapy holds promise for treating triple-negative breast cancer (TNBC). However, the current ADC, sacituzumab govitecan, fails to overcome the crucial role of adenosine in the suppressive immune microenvironment characteristic of this "cold tumor". Here, we present a dual immune-stimulatory complex, αCD73-PLG-MMAE, which targets TNBC specifically and modulates tumor immunity through mechanisms such as immunogenic cell death (ICD) and interference with the adenosine signaling pathway. Thus, it kills tumor cells with cytotoxic drugs, comprehensively regulates immunosuppression, and restores a durable immune response. This study proposes an antibody-polymeric drug complex with immunomodulatory and immunoagonist roles, offering new insights into TNBC treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

This research aimed to create self‐assembled nanogel particles using chitosan grafted with various types of Pluronic to encapsulate curcumin, a hydrophobic biological agent. The study explored the properties of CS–Pluronic nanogels using Pluronic types L61, P123, F127, and F68, each varying in hydrophilic–lipophilic balance (HLB) index. Findings indicated that the critical micelle concentration (CMC) of Pluronics and CS–Pluronic copolymers did not depend on the HLB values but were influenced by the structural characteristics of each Pluronic type. The efficiency of curcumin encapsulation within the nanogels correlated with the CMC values of the CS–Pluronic copolymers, where lower CMC values resulted in higher encapsulation efficiencies. The curcumin‐loaded nanogels were spherical, positively charged, and had an average diameter under 200 nm. Controlled, pH‐dependent release of curcumin was observed in vitro studies conducted at 37°C in PBS at pH levels of 7.4 and 5.0, with a faster release in acidic conditions. Biocompatibility testing indicated that nanogel biocompatibility was influenced by the HLB value of Pluronic, with lower HLB values associated with reduced biocompatibility. Cytotoxicity testing revealed that curcumin‐loaded nanogels had increased cytotoxicity on MCF‐7 cells compared to free curcumin. CS–P123 emerged as the most effective carrier, meeting biocompatibility and stability requirements during storage. Highlights: CS–Pluronic serves as an effective hydrophobic drug delivery system.The capacity of CS–Pluronic to encapsulate hydrophobic drugs is determined by its CMC value rather than its HLB index.CS–Pluronic is a copolymer known for its excellent biocompatibility.CS–Pluronic increases the toxicity of curcumin in nanogels compared to free curcumin. [ABSTRACT FROM AUTHOR]

The malignant form of melanoma is one of the deadliest human cancers that accounts for almost all of the skin tumor-related fatalities in its later stages. Achieving an exhaustive understanding of reliable cancer-specific markers and molecular pathways can provide numerous practical techniques and direct the way toward the development of rational curative medicines to increase the lifespan of patients. Immunotherapy has significantly enhanced the treatment of metastatic and late-stage melanoma, resulting in an incredible increase in positive responses to therapy. Despite the increasing occurrence of melanoma, the median survival rate for patients with advanced, inoperable terminal disease has increased from around six months to almost six years. The current knowledge of the tumor microenvironment (TME) and its interaction with the immune system has resulted in the swift growth of innovative immunotherapy treatments. Exosomes are small extracellular vesicles (EVs), ranging from 30 to 150 nm in size, that the majority of cells released them. Exosomes possess natural advantages such as high compatibility with living organisms and low potential for causing immune reactions, making them practical for delivering therapeutic agents like chemotherapy drugs, nucleic acids, and proteins. This review highlights recent advancements in using exosomes as an approach to providing medications for the treatment of melanoma. [ABSTRACT FROM AUTHOR]

Osteosarcoma is a highly aggressive bone cancer primarily affecting children, adolescents, and young adults. The current gold standard for treatment of osteosarcoma patients consists of two to three rounds of chemotherapy, followed by extensive surgical intervention from total limb reconstruction to amputation, followed by additional rounds of chemotherapy. Although chemotherapy has advanced the treatment of osteosarcoma significantly, the overall 5-year survival rate in resistant forms of osteosarcoma is still below 20%. The interaction between cancer and the immune system has long been recognized as a critical aspect of tumour growth. Tumour cells within the tumour microenvironment (TME) suppress antitumour immunity, and immunosuppressive cells and cytokines provide the extrinsic factors of tumour drug resistance. Emerging research demonstrates an immunostimulatory role for the cGAS/STING pathway in osteosarcoma, typically considered an immune-cold or immunosuppressed cancer type. cGAS/STING signalling appears to drive an innate immune response against tumours and potentiates the efficacy of other common therapies including chemo and radiotherapy. Nanotechnological delivery systems for improved therapy delivery for osteosarcoma have also been under investigation in recent years. This review provides an overview of cGAS/STING signalling, its divergent roles in the context of cancer, and collates current research which activates cGAS/STING as an adjuvant immunomodulatory target for the treatment of osteosarcoma. It will also discuss current nanotechnological delivery approaches that have been developed to stimulate cGAS/STING. Finally, it will highlight the future directions that we believe will be central to the development of this transformative field. [ABSTRACT FROM AUTHOR]

Microbubbles (MB) are widely used as contrast agents for ultrasound (US) imaging and US‐enhanced drug delivery. Polymeric MB are highly suitable for these applications because of their acoustic responsiveness, high drug loading capability, and ease of surface functionalization. While many studies have focused on using polymeric MB for diagnostic and therapeutic purposes, relatively little attention has thus far been paid to improving their inherent imaging and drug delivery features. This study here shows that manipulating the polymer chemistry of poly(butyl cyanoacrylate) (PBCA) MB via temporarily mixing the monomer with the monomer‐mimetic butyl cyanoacetate (BCC) during the polymerization process improves the drug loading capacity of PBCA MB by more than twofold, and the in vitro and in vivo acoustic responses of PBCA MB by more than tenfold. Computer simulations and physisorption experiments show that BCC manipulates the growth of PBCA polymer chains and creates nanocavities in the MB shell, endowing PBCA MB with greater drug entrapment capability and stronger acoustic properties. Notably, because BCC can be readily and completely removed during MB purification, the resulting formulation does not include any residual reagent beyond the ones already present in current PBCA‐based MB products, facilitating the potential translation of next‐generation PBCA MB. [ABSTRACT FROM AUTHOR]

Liver fibrosis, arising from factors such as viral infections or metabolic disorders, represents an ongoing global health challenge and is a major risk factor for hepatocellular carcinoma. Unfortunately, there are no clinically approved drugs available for its treatment. Recent studies have illuminated the pivotal role of macrophage recruitment in the pathogenesis of liver fibrosis, presenting a potential therapeutic target. Therefore, it holds great promise to develop novel anti‐fibrotic therapies capable of inhibiting this process. Herein, a drug‐loaded biomimetic nanodecoy (CNV‐C) is developed by harnessing genetically engineered cellular vesicles for the treatment of liver fibrosis. CNV‐C is equipped with a C‐C motif chemokine receptor 2 (CCR2)‐overexpressed surface, enabling it to selectively neutralize elevated levels of C‐C motif chemokine ligand 2 (CCL2), thereby reducing macrophage infiltration and the subsequent production of the fibrogenic cytokine transforming growth factor β (TGF‐β). Moreover, curcumin, an anti‐fibrotic agent, is loaded into CNV‐C and delivered to the liver, facilitating its efficacy in suppressing the activation of hepatic stellate cells by blocking the downstream TGF‐β/Smad signaling. This combinational therapy ultimately culminates in the alleviation of liver fibrosis in a mouse model induced by carbon tetrachloride. Collectively, the findings provide groundbreaking proof‐of‐concept for employing genetically modified nanodecoys to manage liver fibrosis, which may usher in a new era of anti‐fibrotic treatments. [ABSTRACT FROM AUTHOR]

In this study, a red seaweed (Solieria robusta) containing ι‐carrageenan (Carr) was used for nanoparticles (NPs) synthesis using silver (Ag) ions. Initially, the ι‐Carr was extracted from S. robusta using the alkali method. The Carr extracted was fractionated into 3 fractions and > 14 kDa fraction showing high yield with maximum sulfate content characterized using Fourier transform infrared (FT‐IR) as ι‐Carr was used for AgNPs synthesis. The synthesized CarrAgNPs were again used for curcumin (Cur) encapsulation. The cytotoxicity of Carr, Cur, CarrAgNPs, and CurCarrAgNPs was evaluated using HeLa cell lines by MTT assay. The CarrAgNPs and CurCarrAgNPs were characterized using UV‐visible spectroscopy, as well as FT‐IR and XRD analysis. The UV‐visible spectrum confirms the CarrAgNPs showing characteristic SPR bands recorded between 344 and 490 nm with broad peak at 430 nm. The shape of the NPs is spherical, arranged in order of seven per chain. The XRD and FT‐IR characteristics confirm the orthorhombic crystal structure of these NPs. Remarkably, Cur‐loaded CarrAgNPs demonstrate potent anticancer properties by maximum reduction of HeLa cell viability after 24 h at 200 μg/mL in pH 7.4 in an MTT assay medium. A significant increase in the cancer cell viability was recorded at high concentrations of CurCarrAgNPs, confirming its less diffusion and dissolution properties and bioavailability due to lipophilic Cur encapsulation, whereas cytotoxicity was increased proportionately by increasing concentrations of Cur, Carr, and CarrAgNPs that confirm a direct relation with size, dissolution, and bioavailability recorded on the basis of cell death in 24 h of introduction at pH 7.4. The cytotoxicity results suggest the potential of Cur, Carr, CarrAgNPs, and CurCarrAgNPs for drug delivery in selective biomedical product developments. This study highlights the versatility and effectiveness of CurCarrAgNPs in cancer therapy by enhancing the efficacy of therapeutic interventions and targeted drug delivery. [ABSTRACT FROM AUTHOR]

This study demonstrates a novel nanostructured drug delivery system utilizing α‐Fe2O3/CuO/CuFe2O4 ternary nanocomposite for effective drug transport in sick tissues. Centella Asiatica plant extract was employed to synthesize the Fe2O3/CuO/CuFe2O4 nanocomposite via sol‐gel auto combustion technique. The structural and morphological characteristics of the nanocomposite were investigated by XRD, FT‐IR, SEM, EDX, and VSM for magnetic properties. The XRD analysis demonstrates the successful synthesis of Fe2O3/CuO/CuFe2O4 nanocomposite with an average crystallite size of 18.393 nm. The antioxidant and antifungal capabilities of this nanocomposite were assessed for its biological activity. A notable inhibitory zone was observed when tested against the Alternaria spp. and Bipolaris sorokiniana fungi. An IC50 value of 109.88 μg/ml was found in the DPPH test, indicating that the nanocomposite exhibited remarkable antioxidant characteristics. Subsequently, metronidazole was encapsulated with a success rate of 55.53 % at pH 1.2, while at pH 7.4 it gained 57.83 %. The drug release of nanocomposite at pH 1.2 after 330 min was 43.41 % and at pH 7.4 after 300 min it was 52.3 %. The results indicate its potential as an excellent candidate for drug delivery. Furthermore, pH was found to be an effective catalyst in the drug loading and release processes. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has emerged as a pivotal approach for treating various types of cancer, incorporating strategies such as chimeric antigen receptor T-cell (CAR-T) therapy, immune checkpoint blockade therapy, neoantigen peptides, mRNA vaccines, and small molecule modulators. However, the clinical efficacy of these therapies is frequently constrained by significant adverse effects and limited therapeutic outcomes. In recent years, the integration of nanotechnology into cancer immunotherapy has gained considerable attention, showcasing notable advantages in drug delivery, targeted accumulation, controlled release, and localized administration. This review focuses on nanomaterial-based immunotherapeutic strategies, particularly the development and application of nanocarriers such as liposomes, lipid nanoparticles, polymeric nanoparticles, and self-assembling scaffolds. We examine how these strategies can enhance the efficacy of cancer immunotherapy while minimizing adverse effects and analyze their potential for clinical translation. [ABSTRACT FROM AUTHOR]

Recently developed nanoparticles and nanofibers present new brain‐specific treatment strategies, especially for Alzheimer's disease treatment. In this study, donepezil (DO)‐loaded PLGA nanoparticles (DNP) are embedded in PVA/PEG nanofibers (DNPF) produced by pressurized gyration for sublingual administration. SEM images showed produced drug‐loaded and pure nanofibers, which have sizes between 978 and 1123 nm, demonstrated beadless morphology and homogeneous distribution. FT‐IR, XRD, and DSC results proved the produced nanoparticles and fibers to consist of the DO and other polymers. The in vitro drug release test presented that the release profile of DO is completed at the end of the 18th day. It is released by the first order kinetic model. DNPF has an ultra‐fast release profile via its disintegration within 2 sec, which proved itself to be suitable for the administration sublingually. All samples presented above ≈90% cell viability via their non‐toxic natures on SH‐SY5Y human neuroblastoma cells by using Alamar blue assay. The anti‐Alzheimer effects of DO, DNP, and DNPF are evaluated on the Aβ1−42‐induced SH‐SY5Y cells at 1, 5, and 10 µM as treatment groups. The 1 µM dosage exhibited the most significant neuroprotective effects, which showed enhanced cellular uptake and superior modulation of Alzheimer's‐related proteins, including tau and Aβ. [ABSTRACT FROM AUTHOR]

Introduction: The method of encapsulating the drug molecule in a carrier, such as a magnetic nanoparticle, is a promising development that has the potential to deliver the medicine to the site where it is intended to be administered. Morin is a pentahydroxyflavone obtained from the leaves, stems, and fruits of various plantsmainly from the Moraceae family exhibiting diverse pharmacological activities such as anti-inflammatory, anti-oxidant, and free radical scavenging and helps treat diseases such as diabetes, myocardial infarction and cancer. Methods: In this study, we conducted the synthesis of a nanocomposite with magnetic properties by coating biocompatible activated carbon obtained from okra plant leaves with magnetic nanoparticles. Results: Characterization of the synthesized activated carbon-coated magnetic nanocomposite was confirmed by Fourier transform infrared, scanning electron microscopy, dynamic light scattering, and zeta potential. The cytotoxic effects of the drug-loaded magnetic nanocomposite were examined in HT-29 (Colorectal), MCF-7 (breast), U373 (brain), T98-G (Glioblastoma) cancer cell lines, and human umbilical vein endothelial cells healthy cell line. Discussion: We studied the loading and release behavior of morin hydrate in the activated carbon-coated magnetic nanocomposite. Activated carbon-coated magnetic nanocomposite carriers can show promising results for the delivery of Morin hydrate drugs to the targeted site. [ABSTRACT FROM AUTHOR]

The basic purpose of this work was to develop environmentally friendly, biodegradable, and biocompatible polymeric nanoparticles of sorafenib that can effectively release the desired drug in a customized and controlled manner for targeting hepatocellular carcinoma. The solvent evaporation technique was employed for the synthesis of sorafenib-loaded PLGA-chitosan nanoparticles, followed by various experimental specifications and compatibility studies using poloxamer 407 as the stabilizer. The best nanoparticles thus synthesized were selected to be used for cytotoxicity investigations through in vitro and in vivo assessments. For the in vitro drug release tests, the dialysis bag diffusion technique was used. For both chitosan nanoparticles and PLGA loaded with sorafenib, a biphasic release pattern was found, exhibiting a protracted release lasting 10 days after a 24-h burst release. As experimental animals, rabbits were utilized to evaluate different in vivo pharmacokinetic properties of the selected formulations. Plasma samples were extracted with acetonitrile and analyzed through the developed HPLC method. Pharmacokinetic parameters such as AUC0-t, Cmax MRT, Vd, and half-life (t1/2) were enhanced significantly (p = 0.001), while clearance was considerably decreased (p = 0.001) for the chosen synthesized nanoparticles in contrast to the commercially accessible sorafenib formulation (Nexavar®). The cytotoxicity of the reference drug and sorafenibloaded PLGA and chitosan nanoparticles was calculated by performing an MTT assay against HepG2 cell lines. The developed polymeric sorafenib nanoformulations possess the appropriate physicochemical properties, better targeting, surface morphology, and prolonged release kinetics. The pharmacokinetic parameters were improved significantly when the results were compared with commercially available sorafenib formulations. [ABSTRACT FROM AUTHOR]

Simple Summary: Niclosamide, a drug originally used to treat parasitic infections, has shown potential as a possible cancer treatment, but poor absorptive and solubility properties are believed to limit its effectiveness. Researchers are exploring modified structures of the drug along with advanced delivery methods, particularly nanotechnology, to improve niclosamide's absorption profile and improve its specificity in regard to targeting cancerous cells. These efforts intend to produce more effective tumor-targeting compounds, which can be employed as pharmacological cancer treatment options when appropriate. If successful, these efforts will provide new tools for scientists and doctors, offering a novel approach regarding the treatment of a variety of different cancers and contribute to the elucidation of oncobiology. Inhibition of multiple cancer-related pathways has made niclosamide a promising candidate for the treatment of various cancers. However, its clinical application has been significantly limited by poor bioavailability. This review will discuss current findings on improving niclosamide bioavailability through modification of its chemical structure and utilization of novel nanotechnologies, like electrospraying and supercritical fluids, to improve drug delivery. For example, niclosamide derivatives, such as o-alkylamino-tethered niclosamide derivates, niclosamide ethanolamine salt, and niclosamide piperazine salt, have demonstrated increased water solubility without compromising anticancer activity in vitro. Additionally, this review briefly discusses recent findings on the first pass metabolism of niclosamide in vivo, the role of cytochrome P450-mediated hydroxylation, UDP-glucuronosyltransferase mediated glucuronidation, and how enzymatic inhibition could enhance niclosamide bioavailability. Ultimately, there is a need for researchers to synthesize, evaluate, and improve upon niclosamide derivatives while experimenting with the employment of nanotechnologies, such as targeted delivery and nanoparticle modification, as a way to improve drug administration. Researchers should strive to improve drug-target accuracy, its therapeutic index, and increase the drug's efficacy as an anti-neoplastic agent. [ABSTRACT FROM AUTHOR]

Covalent drugs can offer significant advantages over non-covalent drugs in terms of pharmacodynamics (i.e., target-binding properties). However, the development of covalent drugs is sometimes hampered by pharmacokinetic limitations (e.g., low bioavailability, rapid metabolism and toxicity due to off-target binding). Polymeric nanoparticles offer a potential solution to these limitations. Delivering covalent drugs via polymeric nanoparticles provides myriad benefits in terms of drug solubility, permeability, lifetime, selectivity, controlled release and the opportunity for synergistic administration alongside other drugs. In this short review, we examine each of these benefits in turn, illustrated through multiple case studies. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the major cancer types and poses challenges in its treatment, including lack of specificity and harm to healthy cells. Nanoparticle-based drug delivery systems (NDDSs) show promise in overcoming these challenges. While conventional NDDSs have drawbacks, such as immune response and capture by the reticuloendothelial system (RES), extracellular vesicles (EVs) present a potential solution. EVs, which are naturally released from cells, can evade the RES without surface modification and with minimal toxicity to healthy cells. This makes them a promising candidate for developing a lung-cancer-targeting drug delivery system. EVs isolated from vascular endothelial cells, such as human umbilical endothelial-cell-derived EVs (HUVEC-EVs), have shown anti-angiogenic activity in a lung cancer mouse model; therefore, in this study, HUVEC-EVs were chosen as a carrier for drug delivery. To achieve lung-cancer-specific targeting, HUVEC-EVs were engineered to be decorated with GE11 peptides (GE11-HUVEC-EVs) via a postinsertional technique to target the epidermal growth factor receptor (EGFR) that is overexpressed on the surface of lung cancer cells. The GE11-HUVEC-EVs were loaded with vinorelbine (GE11-HUVEC-EVs-Vin), and then characterized and evaluated in in vitro and in vivo lung cancer models. Further, we examined the binding affinity of ABCB1, encoding P-glycoprotein, which plays a crucial role in chemoresistance via the efflux of the drug. Our results indicate that GE11-HUVEC-EVs-Vin effectively showed tumoricidal effects against cell and mouse models of lung cancer. [ABSTRACT FROM AUTHOR]

This review examines microbial polysaccharides' properties relevant to their use in packaging and pharmaceutical applications. Microbial polysaccharides are produced by enzymes found in the cell walls of microbes. Xanthan gum, curdlan gum, pullulan, and bacterial cellulose are high-molecular-weight substances consisting of sugar residues linked by glycoside bonds. These polysaccharides have linear or highly branched molecular structures. Packaging based on microbial polysaccharides is readily biodegradable and can be considered as a renewable energy source with the potential to reduce environmental impact. In addition, microbial polysaccharides have antioxidant and prebiotic properties. The physico-chemical properties of microbial polysaccharide-based films, including tensile strength and elongation at break, are also evaluated. These materials' potential as multifunctional packaging solutions in the food industry is demonstrated. In addition, their possible use in medicine as a drug delivery system is also considered. [ABSTRACT FROM AUTHOR]

A new concept of biomimetic lubricating nanosystem that realizes long-time lubrication, photothermal responsiveness and anti-inflammation property is developed. High drug loading ratio of 99%, great friction reduction by 75% for more than 7200 times without failure, and effective up-regulation of cartilage anabolic genes and down-regulation of catabolic proteases and pain-related genes are achieved. Our work provides a bioinspired strategy to employ metal organic framework with controlled surface and structure for synergistic therapy of osteoarthritis. [Display omitted] Failure of articular cartilage lubrication and inflammation are the main causes of osteoarthritis (OA), and integrated treatment realizing joint lubrication and anti-inflammation is becoming the most effective treat model. Inspired by low friction of human synovial fluid and adhesive chemical effect of mussels, our work reports a biomimetic lubricating system that realizes long-time lubrication, photothermal responsiveness and anti-inflammation property. To build the system, a dopamine-mediated strategy is developed to controllably graft hyaluronic acid on the surface of metal organic framework. The design constructs a biomimetic core–shell structure that has good dispersity and stability in water with a high drug loading ratio of 99%. Temperature of the solution rapidly increases to 55 °C under near-infrared light, and the hard-soft lubricating system well adheres to wear surfaces, and greatly reduces frictional coefficient by 75% for more than 7200 times without failure. Cell experiments show that the nanosystem enters cells by endocytosis, and releases medication in a sustained manner. The anti-inflammatory outcomes validate that the nanosystem prevents the progression of OA by down-regulating catabolic proteases and pain-related genes and up-regulating genes that are anabolic in cartilage. The study provides a bioinspired strategy to employ metal organic framework with controlled surface and structure for friction reduction and anti-inflammation, and develops a new concept of OA synergistic therapy model for practical applications. [ABSTRACT FROM AUTHOR]

The purpose of the current work was to develop and characterize ethosomes of vitamin D3 gel that could more effectively work against psoriasis. Psoriasis is a chronic immune-mediated inflammatory skin disease. Due to vitamin D3 role in proliferation and maturation of keratinocytes, it has become an important local therapeutic option in the treatment of psoriasis. In this research we have initiated worked on ethosomes gels containing vitamin D3 to treat psoriasis. Soya lecithin 1–8% (w/v), propylene glycol and ethanol were used to create the formulations, which were then tested for vesicle size, shape, surface morphology, entrapment effectiveness, and in vitro drug permeation. The drug encapsulation efficiency of ethosomes was 96.25% ± 0.3. The particle sizes of the optimized ethosomes was 148 and 657 nm, and the PDI value was 0.770 ± 0.12 along with negative charge − 14 ± 3. Fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) along with thermogravimetric analysis (TGA) studies confirmed the absence of interactions between vitamin D3 and other ingredients. It was determined that the total amount of medication that penetrated the membrane was 95.34% ± 3. Percentage lysis was very negligible for all strengths which were found less than 15%. Based on our research, ethosomes appear to be safe for use. The vitamin D3 ethosomal gel order, description, pH, and viscosity were all within the specified ranges, according to the findings of a 6-month investigation into the stability profile of the completed system. In this research, we successfully prepared ethosomes loaded with vitamin D3 and then converted it into gel for patients' easy applications. [ABSTRACT FROM AUTHOR]